We are studying the structure and function of tight junction in kidney epithelial cells grown in culture. The primary emphasis at the present time is to determine to what extent the serine protease plasminogen activator (PA) is involved in the degradation and turnover of tight junctions. For these experiments we are using the tumor promotor phorbol myristate acetate (PMA) to induce high levels of PA synthesis and secretion. At the same time, the PMA causes changes in cell shape that appear to be due to a rearrangement of the epithelial cell cytoskeleton. Through the use of reagents that interact with microtubules and microfilaments and fluorescent antibodies to these structures, we hope to get a clearer picture of PMA inaction with the epithelial cytoskeleton.